Abstract
Brain extraction of two antiepileptic compounds, progabide and its acid metabolite, SL 75102, was investigated using the carotid injection technique in the rat. The extent to which drug binding to plasma proteins could inhibit the brain extraction was measured. Equilibrium dialysis at 4° showed that both drugs were highly bound to human serum proteins, mainly to serum albumin. Progabide is also bound to red blood cells and to lipoproteins. The free dialyzable drug fraction was inversely related to the protein concentration. Similarly, the brain extraction of the drugs in the presence of either albumin, or red blood cells for progabide was inversely related to their respective concentrations. However, the rat brain extraction of both drugs was higher than expected from the in vitro measurement of dialyzable fraction. Furthermore, despite a significant degree of progabide binding to lipoproteins, no significant reduction in the brain extraction of the drug was observed. These data indicate that the amount of circulating progabide or SL 75102 available for penetration in a peripheral tissue such as brain exceeds the dialyzable fraction of drug. However, the in vivo exchangeable drug fraction still parallels the dialyzable fraction, except if the drug is lipoprotein-bound.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
